The ability to provide oxygen to skin tissue is critical for many skin conditions in animals, including wounds, rashes, ulcers, saddle sores, burns, and abrasions. Insufficient oxygenation of compromised tissue will result in slow healing, infections, scar development, and in the worst cases, tissue death and amputation.
The effect of oxygen tension on wound healing has been extensively studied. (For a review, see Whitney, J. D. (1989)). Wound healing is dependent upon several processes including proliferation of fibroblasts, collagen synthesis, angiogenesis and re-epithelialization. Animal studies have shown that several of these processes are affected by the subcutaneous partial pressure of oxygen (O2). For example, supplemental oxygen can lead to increased rate of collagen deposition, epithelialization and improved healing of split thickness grafts. Increased subcutaneous oxygen has also been shown to improve bacterial defenses.
Various methods of administration of oxygen gas in humans, either through inhalation of the gas, or by topical treatment with the gas have been disclosed, including administering oxygen gas to a patient in a hyperbaric chamber.
While a lack of oxygenation can be one cause of skin inflammation in both animals and humans, a second source of causality can be a lowered pH, or reduction, of the skin. While mammalian animals and humans share the same skin compositions and healing processes, mammalian animals sometimes have higher skin pH levels than do humans. For example, healthy horse skin tends to have pH levels around 7.4, and different breeds of dogs can have skin pH levels ranging from approximately 6.8 to 8.6, while the average human skin pH is approximately 4.8. Acidification of skin is associated with diaper rashes and bedsores in humans, and is also associated with conditions such as skin hot spots on dogs and saddle sores on horses, as well as other skin conditions and wounds.
Experts in the veterinary field have long held that alkaline treatments to both human and animal skin make the skin more susceptible to bacterial and fungal infections, such as rain rot and ringworm, as alkaline agents neutralize the skin's acid mantle, which has been seen as critical protection against such infections (see, Skin Deep, by Dr. Eric Witherspoon, TheHorse.com, January 2009, and A sensitive skin to protect, publications.royalcanine com).
Increased pH is also thought to be a symptom of any number of skin conditions, including eczema, contact dermatitis and atypical dermatitis (see, Alkaline pH Skin Problems, Andra Moldav, Apr. 20, 2010). For these reasons, nearly all pH-adjusting skin compositions, both for human and veterinary uses, have tended towards formulation for reduced, not increased, pH.
Dermatitis develops when the skin is subjected to conditions that breakdown the stratum corneum. The stratum corneum is the outer layer of skin and is composed of multiple layers of keratinocytes, with the number of layers varying according to the age and species of animal. The main purpose of this part of the skin is to reduce water loss, repel microbial infection, protect deeper layers, and provide a water-repellant layer. Damage to this layer can occur, for example, when an animal's skin is exposed to agents that lower the skin pH and result in the breakdown of the stratum corneum. Although moisture alone will loosen this layer and allow for friction irritation to occur, breakdown by agents such as urine and fecal enzymes can reduce, or acidify, the skin resulting in chemical irritation. Further, animals are more likely than humans to cause secondary irritation and abrasions by scratching and biting at already-irritated skin.
Environmental hazards such as moisture, contact with bacteria infused water, injuries from skin scratching, shampoo and/or other detergents and skin treatments can cause irritation and hot spots. More specifically, friction or pressure weakens the stratum corneum and eventually causes injury in both humans and animals. These wounds have been found to be at a lower pH than the recognized healthy norm for the relevant animal. Therefore, upward adjustment to the pH of the wound or skin irritation often provides an opportunity for healing. In this regard, the pH levels of skin are comparable to the effects of lowered pH in aquatic environments, which results in lower levels of oxygen content in water, thereby damaging or destroying both aquatic plant and animal life.
Despite the weight of expert opinion in the field against the use of pH-increasing skin products, it is known that increased pH levels and oxygenation promote healing of wounds or skin conditions, whether such conditions arise from external stimuli or from internal processes, such as allergic dermatitis or eczema. In either case, the symptoms may respond positively to a pH raised environment both in counteracting acidification of the skin and in providing increased oxygenation via the higher pH composition.
Pressure-inflicted skin conditions such as saddle sores on horses or collar sores on cats and dogs, like bedsores in human hospital patients, can occur when the skin is exposed to friction, moisture and a lack of oxygenation over an extended period of time. Under such conditions, irritation legions appear at the pressure points on the skin, such as the withers and girth of a horse or neck skin underlying a dog or cat's collar. The wound healing process, depending on the type of injury to the skin, is an intricate process that involves the steps of inflammation, proliferation, and remodeling. During inflammation, bacteria and debris are phagocytized and removed, and factors are released that cause the migration and division of cells involved in the proliferative phase.
The proliferative phase is characterized by angiogenesis, deposition of collagen, formation of granular tissue, re-epithelialization, and wound contraction. In angiogenesis, new blood vessels are formed by vascular endothelial cells. In fibroplasia and formation of granular tissue, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by secreting collagen and fibronectin.
Simultaneously, re-epithelialization occurs, providing a new epithelial layer. It is at this stage that oxygenation of the skin is critical to wound healing.
In the remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis.
Common treatments for the types of skin conditions described hereinabove include use of zinc oxide pastes, powders, petroleum-based creams, and even mild steroid creams to reduce excess moisture, provide antibacterial activity or barriers, and to reduce damage caused by the body's own inflammatory processes. Conventionally, such treatments include a barrier, or “occlusive” component. The purpose of these is to provide a film on the skin and thereby create a layer, which is impermeable to external irritants. Thus, this kind of skin preparation relies on the principle of occlusion, which means that a covering layer is provided on the skin, thereby constituting a certain degree of protection as long as it remains in place. Typically, such occlusive barrier agents are also impermeable to both water and oxygen.
One disadvantage of an occlusive treatment is that even a very small mechanical influence, such as contact that may arise between the skin and clothes, will remove the layer of ointment and thereby eliminate the protecting barrier. Other disadvantages of occlusive barrier ointments are that, due to the impermeability thereof, they increase the body temperature of the user and trap both perspiration and sebum against the skin, thereby further acidifying the skin. Consequently, there is a need of different preparations adapted for different substances, which the user may contact and which are permeable or oxygen and, perhaps, water, while remaining non-permeable to potential irritants.
While some treatments have focused on an antibacterial approach or an approach of keeping skin dry, other have focused on pH. For example, U.S. Pat. No. 6,805,875, to Bartels, discloses topical compositions and treatments of a skin condition in humans commonly known as “diaper rash” and more particularly, acidic-type diaper rash and other skin irritations caused by acidic bodily secretions, usually resulting from teething, antibiotic dosages, bacterial infections, and an acidic diet.
U.S. Pat. No. 6,800,292 to Murad, discloses dermatological agents for treating dermatological disorders, including veterinary use. The dermatological agents include a therapeutically effective amount of at least one fruit extract in an amount sufficient to neutralize free radicals, a moisturizing agent in an amount sufficient to facilitate hydration of the skin, and a pharmaceutically acceptable carrier. Such application teaches the use of inorganic bases, include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc.
U.S. Pat. No. 6,133,318 to Hart, discloses a single medicine oxalic acid or oxalate composition or “magic bullet” and method of treatment or prevention of warm-blooded animals including humans and pets for infectious or pathogenic microbial, bacterial, or viral disease, preventing of bacterial or viral infections, and the like, is provided which includes at least one therapeutically effective form of oxalic acid or oxalate selected from oxalic acid in a free acid, ester, lactone or salt form and oxalate including sodium oxalate, oxalic acid dihydrate, anhydrous oxalic acid, oxamide, and oxalate salts, natural or processed foods including molds, plants or vegetables containing oxalic acid or oxalate, beverages, liquids or juices containing oxalic acid or oxalate, additives containing oxalic acid or oxalate, and combinations thereof.
U.S. Pat. No. 5,993,830 to Friej, discloses a veterinary skin preparation comprising lipophilic and hydrophilic components, which is intended for application on skin. The skin preparation is characterized in that it exists as a two-phase system and it is capable of creating a semi-permeable membrane in the skin.
U.S. Pat. No. 6,328,983 to Afriat, discloses the use of a silicone gum to stabilize ascorbic acid or one of its esters or salts in a topical composition and to novel compositions comprising these components and having an adjustable pH for use in the field of veterinary medicine.
Accordingly, there is still a need for methods and compositions for veterinary treatment of skin injuries that increase the oxygen delivery to the skin and neutralize acidity of the skin in a convenient and efficient manner.